The development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health ...preparations. We retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset. The study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate greater than or equal to25/minute upon hospital presentation, oxygenation <94% on hospital presentation, and pre-hospital comorbidities of hypertension, coronary artery disease, or chronic renal disease. The risk score was highly prognostic of mortality in a training set and confirmatory set yielding in the combined dataset a hazard ratio of 1.80 (95% CI, 1.72, 1.87) for one unit increases. Using observed mortality within 20 equally sized bins of risk scores, a predictive model for an individual's 40-day risk of mortality was generated as -14.258 + 13.460*RS + 1.585*(RS-2.524)^2-0.403*(RS-2.524)^3. An online calculator of this 40-day COVID-19 mortality risk score is available at www.HackensackMeridianHealth.org/CovidRS. A risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective ...prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting.
We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching.
Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available.
In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Carbonic anhydrase IX (CA IX) is a membrane isoenzyme, the overexpression of which is associated with clear cell carcinoma of the kidney. Its overexpression is restricted mainly to cancer, as it is ...absent in corresponding normal tissues making it a potential cancer biomarker. Several recent studies have shown that CA IX, apart from its classical enzyme activity of reversibly hydrating carbon dioxide extracellularly to facilitate the net extrusion of protons from inside to outside the cell, it can also be a key player in the modulation of cell adhesion processes and participate in the regulation of cell proliferation in response to hypoxic environment to ultimately contribute to tumour progression. Here, we have shown that the sole tyrosine moiety of CA IX present in its intracellular domain can be phosphorylated in an epidermal growth factor dependent manner, suggesting that it can feed into the growth factor receptor dependent signalling pathways. Our studies suggest that the tyrosine phosphorylated CA IX can interact with the regulatory subunit of PI-3-Kinase, contributing to Akt activation. These studies have revealed a positive feed back loop that can form the basis of a vicious cycle that could contribute to the progression of clear cell renal carcinoma and poor prognosis. These studies show that CA IX signalling may be a part of both the hypoxia driven and hypoxia independent pathways that occur in the cancer cell. Finally, our studies emphasize the need for a more refined strategy using signal transduction therapeutics to inhibit the cell surface carbonic anhydrases for the management of this malignancy.
Preoperative determination of pathologic outcomes in patients with high-risk prostate cancer is challenging because of limitations of existing nomograms. We aimed to assess whether certain ...preoperative clinical and pathologic characteristics correlate with pathologic outcome in high-risk prostate cancer patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP).
A retrospective evaluation of patients with high-risk disease (prostate-specific antigen PSA >or=10 ng/dL with high volume disease or Gleason score >or=8) who underwent RALP between December 2004 and September 2008 was conducted. Patients were grouped based on favorable pathology, including organ-confined disease and negative surgical margins (group 1), and unfavorable pathology, including positive surgical margins and extracapsular extension (group 2). Preoperative PSA levels, transrectal ultrasonography findings, and biopsy reports were compared to final pathology data.
Of 69 high-risk patients, 37 (54%) had favorable postoperative pathology (group 1) and 32 (46%) had unfavorable pathology (group 2). Mean PSA was 10.0 ng/dL (range, 4.1-20.3) (group 1) and 13.8 ng/dL (range, 3.1-39.9) (group 2). Mean PSA density was 0.28 (group 1) and 0.41 (group 2). Mean positive biopsy core was 33% (group 1) and 44% (group 2). Differences in PSA levels, PSA density, and percentage of positive cores were statistically significant (p < 0.05) between the groups. Bilateral disease and high-grade prostatic intraepithelial neoplasia were not statistically significant (p > 0.05).
Lower PSA level and PSA density, as well as fewer positive biopsy cores, were associated with favorable postoperative pathology. Continued surveillance of these patients will serve to determine whether these findings will assist in predicting which high-risk prostate cancer patients may likely benefit from RALP.
To present extended follow-up on a cohort of patients with renal cortical tumors treated with partial or radical nephrectomy and preoperatively assess for carbonic anhydrase 9 tumor marker expression ...in the peripheral blood.
All patients were originally enrolled in an institutional review board-approved study assessing the role of a reverse-transcriptase polymerase chain reaction peripheral blood assay designed to detect the tumor-specific gene carbonic anhydrase-9 (CA9). A total of 41 patients with renal cortical tumors confined to the kidney were enrolled at a single institution and assessed preoperatively with peripheral blood test for CA9 expression before undergoing partial or radical nephrectomy. A Kaplan-Meier estimated survival analysis and log-rank test were performed to determine whether detection of peripheral blood cells expressing the CA9 gene influences disease-free and disease-specific survival.
The median follow-up was 4.3 years. The median age was 71 years. Of the 41 patients, 26 were men and 15 were women. The estimated 5-year disease-free survival for patients with detectible expression of the CA9 gene in the peripheral blood was 39.5% compared with 88.1% for patients without detection of the CA9 gene (
P = 0.048). On bivariate analysis, disease-free survival correlated with histologic type, tumor diameter, and tumor grade.
The expression of the tumor-specific marker CA9 in the peripheral blood is associated with decreased disease-free survival in patients with renal cortical tumors. This is the first study reporting on the prognostic value of this peripheral blood-based tumor marker for kidney tumors.
Bacillus Calmette-Guérin (BCG) and interferon-α2B (IFN-α2B) have both been individually used for the intravesical treatment of superficial bladder cancer. We report our experience on the therapeutic ...efficacy and toxicity of combined intravesical BCG plus IFN-α2B for treating superficial bladder cancer, including patients failing previous BCG therapy. Thirty-two patients with superficial bladder cancer underwent 6 weekly treatments with full-, one-third, or one-tenth-dose of BCG plus 50 or 100 MU of IFN-α2B based on prior BCG exposure and tolerance. Patients with no evidence of disease proceeded onto maintenance therapy of 3 weekly treatments at 3 months followed by 2 additional maintenance cycles given 6 months apart. Response was assessed by cystoscopy/biopsy every 3 months after treatment. Before BCG plus IFN-α2B treatment, 20 patients (63%) had previously failed intravesical BCG therapy, 27 (84%) had aggressive disease (stage T1, grade 3, or carcinoma in situ), 27 (84%) had recurrent disease, 14 (44%) had multifocal disease, and 6 (19%) had disease of over 4 years duration. At median follow-up of 22 months, 21 patients (66%) remain disease-free and 11 patients (34%) had disease-recurrence. Nineteen of 32 patients (59%) were disease-free after the initial induction cycle. Six of 11 patients 55% ultimately failing combination therapy did so at the first 3 to 4 month evaluation. Four of 7 patients (57%) benefited from salvage re-induction therapy. Of the 20 patients previously treated with BCG, 12 patients (60%) remain disease-free. Combination BCG plus IFN-α2B intravesical therapy was well tolerated. Combination intravesical BCG plus IFN-α2B is an effective and tolerable alternative for patients with superficial bladder cancer, including those patients in whom intravesical BCG therapy had previously failed. Benefits of this combination therapy may include potentially less morbidity, improved clinical efficacy, and in the long term, fewer patients undergoing radical therapy. However, radical treatment options should be pursued for early failures of this combination regimen in those patients with risk factors for recurrence and progression.
The current TNM staging system for renal cortical tumors (RCTs) differentiates between tumors confined to the kidney (T1, T2) and tumors that extend through the renal capsule and invade into the ...perinephric fat (T3a). We examined the relative survival rates of patients with T1 and T3a tumors to determine the accuracy of the current TNM staging classification.
We analyzed the Columbia University Surgical Urological Oncology Database for all patients with clinically localized Stage T1, T2, and T3a RCTs treated surgically from 1988 to 2004. The primary outcomes included local and distant recurrence. Because the T3a classification is not limited by size, we compared T3a tumors with T1 tumors alone and tumors confined within the renal capsule (Stage T1 and T2 tumors combined).
A total of 819 patients underwent partial or radical nephrectomy for RCTs at Columbia University during the study period. After the exclusion criteria were applied, 131 patients with T1N0M0, 19 patients with T2N0M0, and 82 patients with T3aN0M0 conventional renal cell carcinoma were eligible for analysis. The median follow-up was 37 months. The median tumor diameter was 3.2, 3.8, and 5.0 cm for Stage T1, T1 and T2 combined, and T3a lesions, respectively. The estimated 5-year disease-free survival was 95.2% and 90.6% for T1 and T3a RCTs, respectively (
P = 0.922).
Patients with Stage T3a tumors experienced similar outcomes as patients with tumors confined to the renal capsule. These data suggest that the T3a classification should be examined more closely to attempt to improve the prognostic validity of the TNM classification.
Authors from Iowa City report on the incidence of RCC; they compared the rate of these tumours at autopsy and felt that the decrease found was a result of better antemortem detection, and an increase ...with time in the frequency of clinically detected renal cancer.
A study from New York attempted to determine whether size, or transcapsular extension irrespective of size, was more likely to produce an adverse outcome. They analysed their database of 717 such tumours between 1988 and 2002, and found that absolute tumour size was the more significant of the two findings.
OBJECTIVE
To determine which factor was more predictive of adverse outcome in our institutional experience with T2N0M0 and T3N0M0 renal cortical tumours (RCTs) treated surgically, as the current Tumour‐Node‐Metastasis (TNM) staging system for RCTs differentiates between tumours of >7.0 cm but confined to the renal capsule (T2) and tumours that extend through the renal capsule regardless of size (T3a).
MATERIALS AND METHODS
We analysed our institutional database of surgical urological oncology for all patients with T2N0M0 and T3aN0M0 RCT treated with partial or radical nephrectomy from 1988 to 2002. All patients with preoperative metastasis, bilateral or multifocal tumours, nonsporadic disease or benign histology were excluded from analysis. A follow‐up of ≥ 6 months from the time of surgery was required for inclusion. Primary outcomes included local and distant recurrence, and death.
RESULTS
In all, 717 patients had a partial or radical nephrectomy for RCT during the study period. After exclusion criteria were applied, 21 patients with T2N0M0 and 97 with T3aN0M0 tumours were eligible; the median (mean, range) age was 63 (16.6–88.3) years and follow‐up 30.5 (40.8, 6–162) months. The estimated 5‐year disease‐free survival was 68% and 85% for T2N0M0 and T3aN0M0 RCT, respectively (P = 0.002). The 5‐year disease‐specific survival was 81% and 94% for the T2N0M0 and T3aN0M0 groups, respectively (P = 0.085).
CONCLUSION
Patients with T3aN0M0 tumours appear to have better disease‐free and disease‐specific survival than those with T2N0M0 disease, which suggests that tumour invasion through the renal capsule is not as significant as the absolute tumour size.
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